Oxidative Stress And Alcohol Metabolism

Question 1

What organ is responsible for 90% of alcohol?

Where does the rest of the alcohol go?

Answer 1

The liver

The rest is excreted passively in urine and on the breath

Question 2

The first step in alcohol metabolism converts alcohol to what?
What enzyme is necessary to complete this step?

Answer 2

Alcohol—>Acetaldehyde

Alcohol dehydrogenase

Question 3

The second step in alcohol metabolism converts acetaldehyde into what?

Answer 3

Acetaldehyde—>Acetate

Aldehyde dehydrogenase

Question 4

What toxic metabolite is responsible for the “hangover” feeling ?

Answer 4

Acetaldehyde

Question 5

Aldehyde dehydrogenase has a very ________ affinity for acetaldehyde. Why is this is of benefit?

Answer 5

High affinity

It keeps toxic acetaldehyde at very low levels as to not cause damage

Question 6

In what situations might acetaldehyde accumulate in the liver? What can this lead to?

Answer 6

Prolonged, excessive alcohol consumption

Fatty Liver

Question 7

Apart from the accumulation of acetaldehyde, what else can contribute to pathological changes in the liver?

Answer 7

Excess NADH

Increased availability of acetyl-coA

Question 8

What drug can be used to treat those with a dependency to alcohol by causing “hangover” effects in those that continue to drink whilst taking it?

Answer 8

Disulfiram

Question 9

What are ROS and RNS?

Answer 9

Free radicals which are atoms or molecules with one or more UNPAIRED electrons capable of independent existence

Question 10

What is the problem with ROS and RNS being around the body? How to they cause damage?

Answer 10

They are highly reactive and generate more radials, with the potential to cause damage
Damage: Nucleic acids, proteins and lipids

Question 11

How do free radials damage nucleic acids, proteins and lipids?

Answer 11

Nucleic acids: Cause strand break mutations in sugar cause mismatch mutation in base
Proteins: Disulphide bond formation and degradation
Lipids: Disrupt membrane integrity

Question 12

What are some endogenous and exogenous sources of free radials?

Answer 12

Endogenous: 
-Electron transport chain 
-Nitric oxide synthases (NOS) 
-NADPH oxidases- (Resp. burst) 
Exogenous: 
-Radiation 
-Pollutants
-Drugs 
-Toxins

Question 13

Name the three most relevant free radials that might cause damage in the body
Which is the most damaging?

Answer 13

Superoxide O2-‘
Hydroxyl radical OH’ - MOST DAMAGING
Nitric oxide NO’ (also needed for signalling)
Hydrogen peroxide H2O2 (not a free radial but reacts to form them)

Question 14

What cellular defences help to protect against free radicals?

Answer 14

Superoxide dismutase (SOD) / Catalase
Glutathione
Free radical scavengers - vitamin E and C

Question 15

How does superoxide dismutase and catalase neutralise superoxide?

Answer 15

Superoxide dismutase creates H2O2 and O2 from superoxide

Catalase converts the H2O2 into H20 and O2

Question 16

How does glutathione (GSH) protect against ROS?

What does this reaction require?

Answer 16

Donates an electron to ROS and forms a disulphide bond with another glutathione (GSH)
Requires selenium

Question 17

How do vitamins E and C protect against free radicals?

Answer 17

They donate a H+ atom and an electron to free radicals

Question 18

What is galactosaemia?

Answer 18

A deficiency in any of the 3 enzymes required for metabolism of galactose

Question 19

How are individuals with galactosaemia susceptible to damage from free radicals?

Answer 19

Increased activity of aldose reductase consumes excess NADPH which compromises ROS defences and allows free radials to cause damage

Question 20

What is the importance of of G6PDH deficiency in its contribution to damage by free radials?

Answer 20

G6PDH is a rate limiting enzyme for the pentose phosphate pathway, deficiency means there is less protection against oxidative stress causes lipid perioxidation, haemolysis and protein changes

Question 21

What is the name given to the precipitation of haemoglobin as a result of G6PDH deficiency?

Answer 21

Heinz bodies

Question 22

What is the mechanism by which paracetamol elicits its toxic effects?

Answer 22

Produces NAPQI which is a toxic metabolite that damages hepatocytes
Liver uses up the glutathione in an attempt to help the damage which leads to depletion

Question 23

What is the antidote for paracetamol overdose?

How does this drug try to reverse the toxic effect of paracetamol?

Answer 23

Acetylcysteine

Replenishes the glutathione which binds to and inactivates the toxic metabolite